Hypercholesterolemia is known to be one of the prime risk factors for ischemic cardiovascular disease such as arteriosclerosis. To date, there is still no effective antihypercholesterolemic agent commercially available that has found wide patient acceptance. The bile acid sequestrants seem to be moderately effective but they must be consuemd in large quantities, i.e., several grams at a time and they are not very palatable.
There are agents known, however, that are very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. These agents include the natural fermentation products compactin and mevinolin and a variety of semisynthetic and totally synthetic analogs thereof. The naturally occurring compounds and their semisynthetic analogs have the following general structural formulae: ##STR2## wherein:
Z is hydrogen, C.sub.1-5 alkyl or C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino;
R is: ##STR3## wherein Q is ##STR4##
R.sub.2 is H or OH:
R.sub.1 is hydrogen or methyl; and a, b, c, and d represent optional double bonds, specially where b and d represent double bonds or a, b, c, and d are all single bonds.
U.S. Pat. No. 4,517,373 discloses semisynthetic compounds represented by the above general formula wherein R is ##STR5##
U.S. Pat. Nos. 4,346,227 and 4,448,979 also disclose semi-synthetic compounds represented by the above general formula wherein R is ##STR6##
Japanese unexamined patent application J59-122,483-A discloses a semi-synthetic compound represented by the above general formula wherein R is ##STR7## in which R.sub.3 is hydrogen or methyl; R.sub.4 is hydrogen, halogen or haloalkyl; R.sub.5 is hydrogen, halogen or loweralkyl and R.sub.6 is halogen, N.sub.3, hydroxy, thio, amino, lower alkoxy, lower alkylthio and aralkylthio.
U.S. Pat. No. 4,444,784 discloses 8'-acyloxy derivatives of compactin, mevinolin and the dihydro and tetrahydro analogs thereof. Generically disclosed are the compounds represented by the above general formula wherein R is ##STR8## in which R.sub.7 is hydrogen or methyl and R.sub.8 l is C.sub.3-10 cycloalkyl.